CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY

心脏肥大的细胞机制

• 批准号: 3097785
• 负责人: EUGENE MORKIN
• 金额: $ 70.06万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097785
• 关键词: cellular pathology; heart enlargement; heart failure; muscle proteins; myosin light chain kinase; neuropeptides

This proposal is a multidisciplinary study of the cellular and biochemical basis for alterations in the mechanical performance of the hypertrophied and failing hearts. Several animals models will be studied, including the rat post-infarction heart failure model, the spontaneously hypertensive rat, and a mouse model of Coxsackievirus B myocarditis. In this renewal application, we will focus our investigations on five general areas: 1) Molecular mechanisms in the regulation of myosin heavy chain gene_expression, including the effects of thyroid hormone and mechanical stretch. 2) The role of the autonomic nervous system and other neurohumoral factors in the modulation of cardiac growth and performance. 3) The regulation of contraction in vascular smooth muscle with emphasis on structure-function relationships in smooth muscle myosin and myosin light chain kinase. 4) Comparison of treatment with thyromimetic agents versus more conventional therapy in the rat post-infarction heart failure model to examine the hypothesis that switching from a low to a high activity cardiac myosin isoform might be a worthwhile strategy in the management of heart failure. 5) The role of cell- mediated immunity in murine Coxsackievirus B myocarditis will be investigated with the goal of developing a rational basis for treatment of human viral myocarditis. Investigators within the institution will combine their resources, using common animal models to explore fundamental mechanisms involved in hypertrophy and failure. This proposal represents a continuation of collaborative efforts that already are underway in various laboratories. Mechanisms have been established for communication of data, critical review of research in progress and administrative control of all aspects of this project.

该建议是对细胞和细胞的多学科研究 改变机械性能的生化基础 肥厚和失败的心。 几种动物模型将 被研究，包括大鼠炎后心力衰竭模型， 自发性高血压大鼠和小鼠模型 Coxsackievivirus B心肌炎。 在此续订应用程序中，我们将 将我们的调查集中在五个一般领域：1）分子 肌球蛋白重链gene_expression调节中的机制， 包括甲状腺激素和机械拉伸的作用。 2）自主神经系统和其他神经瘤的作用 心脏增长和性能调节的因素。 3） 调节血管平滑肌中收缩的调节 强调平滑肌的结构功能关系 肌球蛋白和肌球蛋白轻链激酶。 4）治疗的比较 与甲状腺胶质剂相对于更常规的治疗 大鼠孔后心力衰竭模型检查假设 从低活动转换为高活动心脏肌球蛋白同工型 在管理心力衰竭方面，可能是值得的策略。 5）细胞介导的免疫力在鼠Coxsackievivirus B中的作用 心肌炎将进行研究，目的是开发 治疗人类病毒心肌炎的合理基础。 机构中的调查人员将结合其资源， 使用常见的动物模型探索基本机制 参与肥大和失败。 该建议代表 延续已经正在进行的协作努力 各种实验室。 已经建立了机制 数据的沟通，对正在进行的研究的批判性审查以及 该项目各个方面的行政控制。